Aims: To evaluate the possible relationship between occupational and environmental exposure to pesticides and solvents that act as carriers for the pesticides and adverse reproductive outcomes and impaired neurologic function. Procedures and techniques: There are two projects I am working on concerning pesticides. One is the Worker's Health study, a study of neurologic function among farmworkers chronically exposed to pesticides. In the other I am analyzing data on the reproductive health of farm women in the Agricultural health study. For the worker's health study, I am taking the lead on analyses on exposure assessment and on the relationship between genetic susceptibility to organophosphate pesticides and neurologic function. Using DNA collected from cheek swabs we will analyze the relationship between two polymorphisms (PON1 and PON2), chronic pesticide exposure and risk of subclinical neurological deficits. These paraoxonase polymorphisms are believed to play a role in mediating oxidative stress in heart disease and in the metabolism of organophosphate pesticides. For the Agricultural health study, I am analyzing data on the relationship between pesticide and other farm exposures and menstrual cycle abnormalities, and fetal loss among women living on farms. I am also working on developing methods to improve questionnaire assessment of pesticide exposure by collecting information on occupational pesticide hygiene. Accomplishments: I have completed analyses that look at the relationship between cumulative days of insecticide use and risk of pesticide poisoning, risk of seeing a doctor because of pesticide related symptoms, risk of feeling nausea or feeling chest tightening after using insecticides. For each of these four outcomes there was a strong relationship with cumulative insecticide exposure. However, adding the farmer's pesticide hygiene score significantly improved the statistical fit of each of these models suggesting that regardless of outcome, using data on pesticide hygiene contributes important information to the models. Because this information is relatively easy to collect, it offers a methodology for improving questionnaire data on occupational pesticide exposure. As a first step in analyzing the data on the relationship between pesticide exposure and risk of changes in menstrual cycle function, I conducted an analysis of medical and lifestyle factors associated with different menstrual cycle patterns. We restricted the analysis to about 4200 premenopausal women age 21-40 who were not taking oral contraceptives, were not currently pregnant or breast feeding. We found that age, BMI, age at menarche, cigarette smoking, history of Grave's disease, depression requiring medication were associated with changes in menstrual cycle function. Body mass was linearly associated with long or irregular cycles for each of five BMI groups above the reference category of BMI of 22-23; few studies had previously shown such a strong relationship between body mass and menstrual cycle function even among non-obese women. We also found a relationship between menstrual cycle patterns and history of infertility and spontaneous abortion. Recognizing the limitations of cross-sectional data, we tentatively interpret this to suggest that factors that disrupt menstrual cycle function may interfere with other reproductive outcomes. The Workers' Health Study Through focus groups with farmworkers, walk-through inspections of nurseries, greenhouses and fern fields, and consultations with industrial hygienists from NIOSH, academic occupational health experts, U.S. Department of Agriculture crop inspectors, and agricultural extension agents and crop scientists at the University of Florida and North Carolina State University, I identified key components of the daily tasks of farmworkers in the three crops of interest. We incorporated questions about these tasks and about pesticide hygiene practices into our exposure assessment strategy. The study was completed in 1998. Buccal cells were obtained from study participants using cheek swabs. Six swabs were collected from each participant and stored in alcohol. DNA was extracted from 3 of these swabs for each person. Genotyping began this year. We were able to successfully genotype PON_192. About a quarter of the participants were homozygous for the high activity allele, fifty percent were heterozygous, and about 25% were homozygous for the low activity (highest) risk allele.